Abstract
Purpose :
Neuroinflammation is increasingly implicated in glaucoma pathogenesis. We previously showed that decreasing macrophage/microglia activation and astrogliosis rescued retinal ganglion cells (RGCs) following intraocular pressure (IOP) elevation in mice (PMID33147455). Our findings also suggest monocyte infiltration may drive astrogliosis. Using the microbead occlusion model of glaucoma, we examined the association between RGC death and the distribution of retinal myeloid cells following IOP elevation.
Methods :
Microbead injections were used to elevate IOP as previously described (PMID32045598). Briefly, 4-month-old C57BL/6J mice received injections of magnetic microbeads in the anterior chamber of one eye while the contralateral eye received sterile balanced salt solution (BSS). Mice were injected on days 0 and 16. IOP was measured immediately prior to the first injection, 4 days post-injection, and then weekly thereafter. After 6 weeks, immunolabeling of retina flat-mounts for RBPMS and Iba1 was used to quantify cellular density [cells per 63x high-power field (HPF)] of RGCs and myeloid cells, respectively, in the central and peripheral retina.
Results :
IOP remained elevated for 6 weeks following microbead injections (Mean±SEM 15.4±0.3mmHg vs. BSS 11.9±0.2, p<0.0001). After 6 weeks, RGC density was lower in microbead vs. BSS eyes (107.1±2.9 vs. 124.3±2.5, p<0.05). In contrast, myeloid cell (Iba1+) density was higher in microbead vs. BSS eyes (4.0±0.1 vs. 2.8±0.1, p<0.001; Fig. 1). Interestingly, in microbead eyes, higher central myeloid cell density was correlated with lower RGC density, particularly in the periphery (R=0.14, p<0.0001). The same correlation was not observed in BSS eyes.
Conclusions :
Results support increased macrophage/microglia activation in response to ocular hypertension. The correlation between higher central macrophage/microglia density and greater RGC loss suggests that increased central activation and/or monocyte extravasation from the optic nerve are important drivers of RGC death. Examining for evidence of monocyte infiltration immediately after IOP elevation will expand upon this finding.
This is a 2021 ARVO Annual Meeting abstract.